1,965 research outputs found
International Entrepreneurs' Performance-Orientation and their Social Capital for Internationalization
Interpreting Measurements of Small Strain Elastic Shear Modulus under Unsaturated Conditions
Bender element testing of unsaturated isotropically compacted speswhite kaolin samples was used to investigate the variation of small strain elastic shear modulus G under unsaturated conditions. Testing was performed in a suction-controlled triaxial cell and involved combinations of isotropic loading and unloading stages and wetting and drying stages. Analysis of the experimental results indicated that the variation of G could be represented by a simple expression involving only mean Bishop’s stress p* and specific volume v, with the only significant mismatches between measured and predicted values of G occuring at the end of final unloading. No significant improvement of fit was achieved by incorporating additional dependency on degree of saturation Sr or a bonding parameter ζ. The proposed expression for G reverts to a well-established form for saturated soils as Sr tends to 1
Influence of Mechanical Yielding on Predictions of Saturation: The Saturation Line
It is now well accepted that the mechanical and the water retention behaviour of a soil under unsaturated conditions are coupled and, that such coupling, should be incorporated into a constitutive model for a realistic representation of soil’s response. In existing models, the influence of the mechanical behaviour on the water retention is often represented by a shift of the main wetting retention curve to higher values of matric suction (the difference between pore air and pore water pressures) when the specific volume decreases. This means that any variation of total volumetric strains of compression (whether these are elastic or elasto-plastic) will result in a shift of the main wetting and drying curves to the right, when these curves are represented in the water retention plane. This shift of the main water retention curves, however, should not only influence the unsaturated stress states as often described in the literature, it should also have some impact on the saturated stress states and, more specifically, on the predictions of de-saturation (air-entry point) and saturation (air-exclusion point). From a modelling point of view, it is advantageous to represent this influence through the plastic component of volumetric strain of compression only because, in this way, a consistent representation of the mechanical behaviour for both unsaturated and saturated states can be naturally achieved. This and other advantages resulting from this singular approach are demonstrated in the paper in the context of the Glasgow Coupled Model (GCM)
Network modelling of the influence of swelling on the transport behaviour of bentonite
Wetting of bentonite is a complex hydro-mechanical process that involves swelling and,
if confined, significant structural changes in its void structure. A coupled structural transport network
model is proposed to investigate the effect of wetting of bentonite on retention conductivity and
swelling pressure response. The transport network of spheres and pipes, representing voids and
throats, respectively, relies on Laplace–Young’s equation to model the wetting process. The structural
network uses a simple elasto-plastic approach without hardening to model the rearrangement of
the fabric. Swelling is introduced in the form of an eigenstrain in the structural elements, which are
adjacent to water filled spheres. For a constrained cell, swelling is shown to produce plastic strains,
which result in a reduction of pipe and sphere spaces and, therefore, influence the conductivity and
retention behaviour
Network Modelling of Fluid Retention Behaviour in Unsaturated Soils
The paper describes discrete modelling of the retention behaviour of unsaturated porous materials. A network approach is used within a statistical volume element (SVE), suitable for subsequent use in hydro-mechanical analysis and incorporation within multi-scale numerical modelling. The soil pore structure is modelled by a network of cylindrical pipes connecting spheres, with the spheres representing soil voids and the pipes representing inter-connecting throats. The locations of pipes and spheres are determined by a Voronoi tessellation of the domain. Original aspects of the modelling include a form of periodic boundary condition implementation applied for the first time to this type of network, a new pore volume scaling technique to provide more realistic modelling and a new procedure for initiating drying or wetting paths in a network model employing periodic boundary conditions. Model simulations, employing two linear cumulative probability distributions to represent the distributions of sphere and pipe radii, are presented for the retention behaviour reported from a mercury porosimetry test on a sandstone
Hydro-mechanical network modelling of particulate composites
Differential shrinkage in particulate quasi-brittle materials causes
microcracking which reduces durability in these materials by increasing their
mass transport properties. A hydro-mechanical three-dimensional periodic
network approach was used to investigate the influence of particle and specimen
size on the specimen permeability. The particulate quasi-brittle materials
studied here consist of stiff elastic particles, and a softer matrix and
interfacial transition zones between matrix and particles exhibiting nonlinear
material responses. An incrementally applied uniform eigenstrain, along with a
damage-plasticity constitutive model, are used to describe the shrinkage and
cracking processes of the matrix and interfacial transition zones. The results
showed that increasing particle diameter at constant volume fraction increases
the crack widths and, therefore, permeability, which confirms previously
obtained 2D modelling results. Furthermore, it was demonstrated that specimen
thickness has, in comparison to the influence of particle size, a small
influence on permeability increase due to microcracking
On the roles and sub-cellular localisations of lipids in neurodegenerative disorders
Niemann-Pick type C disease (NPCD) is a ruinous condition that mostly affects children. Although stemming from a single genetic error its pathology involves dysfunction of multiple organs especially liver, spleen and brain. Life expectancy is dramatically reduced.
NPCD is usually caused by a mutation in NPC1 a protein located in the lysosome, the cell’s recycling centre, and believed to export cholesterol from there for use elsewhere in the cell. Consequently NPCD patients accumulate cholesterol in their lysosomes. Extensive research has found that mutation of this single protein restricted to one organelle has effects that encompass almost every aspect of cellular function. This is rather surprising so chapter 1 attempts to piece together what we know to give as coherent and complete an account as possible of the cellular pathology of this disease including insights gathered from the various treatment approaches tried to date.
Using a combined docking-molecular dynamics approach Chapter 2 supports the idea, previously advanced from in vitro experiments, that NPC1 and its partner NPC2 may also bind sphingosine, the simplest sphingolipid. This chapter also uses docking to understand some previously observed, but not fully explained, aspects of lysosomal dysfunction in NPCD including reduced big potassium channel activity, annexin mislocalisation and impaired SNARE recycling. These errors are traced ultimately to cholesterol accumulation but pathological roles are found for other lipids which also accumulate in this disease
Chapter 3 finds that lysosomal pH is increased in fibroblasts from NPC1-deficient patient fibroblasts; inhibtion of glucocerbrosidase 2 (GBA2), the only clinically approved NPCD treatment, corrects this error. The same treatment is not effective in other Niemann-Pick variants. Only limited and preliminary success was encounted when GBA2 inhibition was examined as a potential treatment for related diseases.
Chapter 4 finds that the mitochondrial defect in NPCD is not responsive to GBA2 inhibition nor to manipulation of sphingolipids more widely. Attempts at correcting this error by manipulating mitochondrial cholesterol, widely believed to be elevated to levels toxic to this organelle, were not clearly effective.
Chapter 5 draws the various threads of this thesis together and combines them with very recent work published elsewhere to sketch an integrated cellular pathology of NPCD
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